Skip to main content
Top
Published in: Journal of Neural Transmission 8/2010

Open Access 01-08-2010 | Basic Neurosciences, Genetics and Immunology - Review Article

Macrophages in Alzheimer’s disease: the blood-borne identity

Authors: David Gate, Kavon Rezai-Zadeh, Dominique Jodry, Altan Rentsendorj, Terrence Town

Published in: Journal of Neural Transmission | Issue 8/2010

Login to get access

Abstract

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder clinically characterized by cognitive decline involving loss of memory, reasoning and linguistic ability. The amyloid cascade hypothesis holds that mismetabolism and aggregation of neurotoxic amyloid-β (Aβ) peptides, which are deposited as amyloid plaques, are the central etiological events in AD. Recent evidence from AD mouse models suggests that blood-borne mononuclear phagocytes are capable of infiltrating the brain and restricting β-amyloid plaques, thereby limiting disease progression. These observations raise at least three key questions: (1) what is the cell of origin for macrophages in the AD brain, (2) do blood-borne macrophages impact the pathophysiology of AD and (3) could these enigmatic cells be therapeutically targeted to curb cerebral amyloidosis and thereby slow disease progression? This review begins with a historical perspective of peripheral mononuclear phagocytes in AD, and moves on to critically consider the controversy surrounding their identity as distinct from brain-resident microglia and their potential impact on AD pathology.
Literature
go back to reference Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10(12):1538–1543CrossRefPubMed Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10(12):1538–1543CrossRefPubMed
go back to reference Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117(2):145–152CrossRefPubMed Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117(2):145–152CrossRefPubMed
go back to reference Attems J, Jellinger KA, Lintner F (2005) Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol 110(3):222–231CrossRefPubMed Attems J, Jellinger KA, Lintner F (2005) Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol 110(3):222–231CrossRefPubMed
go back to reference Beers DR, Henkel JS, Zhao W, Wang J, Appel SH (2008) CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci USA 105(40):15558–15563CrossRefPubMed Beers DR, Henkel JS, Zhao W, Wang J, Appel SH (2008) CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci USA 105(40):15558–15563CrossRefPubMed
go back to reference Boissonneault V, Filali M, Lessard M, Relton J, Wong G, Rivest S (2009) Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer’s disease. Brain 132(4):1078–1092CrossRefPubMed Boissonneault V, Filali M, Lessard M, Relton J, Wong G, Rivest S (2009) Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer’s disease. Brain 132(4):1078–1092CrossRefPubMed
go back to reference Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290(5497):1775–1779CrossRefPubMed Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290(5497):1775–1779CrossRefPubMed
go back to reference Butovsky O, Koronyo-Hamaoui M, Kunis G, Ophir E, Landa G, Cohen H, Schwartz M (2006) Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc Natl Acad Sci USA 103(31):11784–11789CrossRefPubMed Butovsky O, Koronyo-Hamaoui M, Kunis G, Ophir E, Landa G, Cohen H, Schwartz M (2006) Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc Natl Acad Sci USA 103(31):11784–11789CrossRefPubMed
go back to reference Butovsky O, Kunis G, Koronyo-Hamaoui M, Schwartz M (2007) Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer’s disease model. Eur J Neurosci 26(2):413–416CrossRefPubMed Butovsky O, Kunis G, Koronyo-Hamaoui M, Schwartz M (2007) Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer’s disease model. Eur J Neurosci 26(2):413–416CrossRefPubMed
go back to reference Chakrabarty P, Jansen-West K, Beccard A, Ceballos-Diaz C, Levites Y, Verbeeck C, Zubair AC, Dickson D, Golde TE, Das P (2010) Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition. FASEB J 24(2):548–559CrossRefPubMed Chakrabarty P, Jansen-West K, Beccard A, Ceballos-Diaz C, Levites Y, Verbeeck C, Zubair AC, Dickson D, Golde TE, Das P (2010) Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition. FASEB J 24(2):548–559CrossRefPubMed
go back to reference Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, Carroll MC (2008) T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci USA 105(46):17913–17918CrossRefPubMed Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, Carroll MC (2008) T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci USA 105(46):17913–17918CrossRefPubMed
go back to reference Colton CA (2009) Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 4(4):399–418CrossRefPubMed Colton CA (2009) Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 4(4):399–418CrossRefPubMed
go back to reference Czlonkowska A, Kurkowska-Jastrzebska I, Czlonkowski A, Peter D, Stefano GB (2002) Immune processes in the pathogenesis of Parkinson’s disease—a potential role for microglia and nitric oxide. Med Sci Monit 8(8):RA165–RA177PubMed Czlonkowska A, Kurkowska-Jastrzebska I, Czlonkowski A, Peter D, Stefano GB (2002) Immune processes in the pathogenesis of Parkinson’s disease—a potential role for microglia and nitric oxide. Med Sci Monit 8(8):RA165–RA177PubMed
go back to reference Dickson DW (1999) Microglia in Alzheimer’s disease and transgenic models. How close the fit? Am J Pathol 154(6):1627–1631PubMed Dickson DW (1999) Microglia in Alzheimer’s disease and transgenic models. How close the fit? Am J Pathol 154(6):1627–1631PubMed
go back to reference Drevets DA, Dillon MJ, Schawang JS, Van Rooijen N, Ehrchen J, Sunderkotter C, Leenen PJ (2004) The Ly-6Chigh monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice. J Immunol 172(7):4418–4424PubMed Drevets DA, Dillon MJ, Schawang JS, Van Rooijen N, Ehrchen J, Sunderkotter C, Leenen PJ (2004) The Ly-6Chigh monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice. J Immunol 172(7):4418–4424PubMed
go back to reference Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94(8):4080–4085CrossRefPubMed Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94(8):4080–4085CrossRefPubMed
go back to reference El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13(4):432–438CrossRefPubMed El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13(4):432–438CrossRefPubMed
go back to reference Ellis RJ, Olichney JM, Thal LJ, Mirra SS, Morris JC, Beekly D, Heyman A (1996) Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CERAD experience, Part XV. Neurology 46(6):1592–1596PubMed Ellis RJ, Olichney JM, Thal LJ, Mirra SS, Morris JC, Beekly D, Heyman A (1996) Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CERAD experience, Part XV. Neurology 46(6):1592–1596PubMed
go back to reference Flaris NA, Densmore TL, Molleston MC, Hickey WF (1993) Characterization of microglia and macrophages in the central nervous system of rats: definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction. Glia 7(1):34–40CrossRefPubMed Flaris NA, Densmore TL, Molleston MC, Hickey WF (1993) Characterization of microglia and macrophages in the central nervous system of rats: definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction. Glia 7(1):34–40CrossRefPubMed
go back to reference Frackowiak J, Wisniewski HM, Wegiel J, Merz GS, Iqbal K, Wang KC (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol 84(3):225–233CrossRefPubMed Frackowiak J, Wisniewski HM, Wegiel J, Merz GS, Iqbal K, Wang KC (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol 84(3):225–233CrossRefPubMed
go back to reference Fujinami RS, Oldstone MB (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230(4729):1043–1045CrossRefPubMed Fujinami RS, Oldstone MB (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230(4729):1043–1045CrossRefPubMed
go back to reference Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71–82CrossRefPubMed Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71–82CrossRefPubMed
go back to reference Graeber MB, Streit WJ, Buringer D, Sparks DL, Kreutzberg GW (1992) Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain. J Neuropathol Exp Neurol 51(3):303–311CrossRefPubMed Graeber MB, Streit WJ, Buringer D, Sparks DL, Kreutzberg GW (1992) Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain. J Neuropathol Exp Neurol 51(3):303–311CrossRefPubMed
go back to reference Grathwohl SA, Kalin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S et al (2009) Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 12(11):1361–1363CrossRefPubMed Grathwohl SA, Kalin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S et al (2009) Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 12(11):1361–1363CrossRefPubMed
go back to reference Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11(3):328–334CrossRefPubMed Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11(3):328–334CrossRefPubMed
go back to reference Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12(10):383–388CrossRefPubMed Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12(10):383–388CrossRefPubMed
go back to reference Hawkes CA, McLaurin J (2009) Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci USA 106(4):1261–1266CrossRefPubMed Hawkes CA, McLaurin J (2009) Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci USA 106(4):1261–1266CrossRefPubMed
go back to reference Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW et al (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372(9634):216–223CrossRefPubMed Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW et al (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372(9634):216–223CrossRefPubMed
go back to reference Huell M, Strauss S, Volk B, Berger M, Bauer J (1995) Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer’s disease patients. Acta Neuropathol 89(6):544–551CrossRefPubMed Huell M, Strauss S, Volk B, Berger M, Bauer J (1995) Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer’s disease patients. Acta Neuropathol 89(6):544–551CrossRefPubMed
go back to reference Jellinger KA, Attems J (2008) Cerebral amyloid angiopathy in Lewy body disease. J Neural Transm 115(3):473–482CrossRefPubMed Jellinger KA, Attems J (2008) Cerebral amyloid angiopathy in Lewy body disease. J Neural Transm 115(3):473–482CrossRefPubMed
go back to reference Jücker M, Heppner FL (2008) Cerebral and peripheral amyloid phagocytes—an old liaison with a new twist. Neuron 59(1):8–10CrossRefPubMed Jücker M, Heppner FL (2008) Cerebral and peripheral amyloid phagocytes—an old liaison with a new twist. Neuron 59(1):8–10CrossRefPubMed
go back to reference Juedes AE, Ruddle NH (2001) Resident and infiltrating central nervous system APCs regulate the emergence and resolution of experimental autoimmune encephalomyelitis. J Immunol 166(8):5168–5175PubMed Juedes AE, Ruddle NH (2001) Resident and infiltrating central nervous system APCs regulate the emergence and resolution of experimental autoimmune encephalomyelitis. J Immunol 166(8):5168–5175PubMed
go back to reference Kennedy DW, Abkowitz JL (1998) Mature monocytic cells enter tissues and engraft. Proc Natl Acad Sci USA 95(25):14944–14949CrossRefPubMed Kennedy DW, Abkowitz JL (1998) Mature monocytic cells enter tissues and engraft. Proc Natl Acad Sci USA 95(25):14944–14949CrossRefPubMed
go back to reference King IL, Dickendesher TL, Segal BM (2009) Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 113(14):3190–3197CrossRefPubMed King IL, Dickendesher TL, Segal BM (2009) Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 113(14):3190–3197CrossRefPubMed
go back to reference Kiyota T, Yamamoto M, Xiong H, Lambert MP, Klein WL et al (2009) CCL2 accelerates microglia-mediated Aβ oligomer formation and progression of neurocognitive dysfunction. PLoS ONE 4(7):e6197CrossRefPubMed Kiyota T, Yamamoto M, Xiong H, Lambert MP, Klein WL et al (2009) CCL2 accelerates microglia-mediated Aβ oligomer formation and progression of neurocognitive dysfunction. PLoS ONE 4(7):e6197CrossRefPubMed
go back to reference Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM (2000) Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol 103(1):97–102CrossRefPubMed Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM (2000) Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol 103(1):97–102CrossRefPubMed
go back to reference Liu K, Waskow C, Liu X, Yao K, Hoh J, Nussenzweig M (2007) Origin of dendritic cells in peripheral lymphoid organs of mice. Nat Immunol 8(6):578–583CrossRefPubMed Liu K, Waskow C, Liu X, Yao K, Hoh J, Nussenzweig M (2007) Origin of dendritic cells in peripheral lymphoid organs of mice. Nat Immunol 8(6):578–583CrossRefPubMed
go back to reference Liu J, Gong N, Huang X, Reynolds AD, Mosley RL, Gendelman HE (2009) Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration. J Immunol 182(6):3855–3865CrossRefPubMed Liu J, Gong N, Huang X, Reynolds AD, Mosley RL, Gendelman HE (2009) Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration. J Immunol 182(6):3855–3865CrossRefPubMed
go back to reference Massengale M, Wagers AJ, Vogel H, Weissman IL (2005) Hematopoietic cells maintain hematopoietic fates upon entering the brain. J Exp Med 201(10):1579–1589CrossRefPubMed Massengale M, Wagers AJ, Vogel H, Weissman IL (2005) Hematopoietic cells maintain hematopoietic fates upon entering the brain. J Exp Med 201(10):1579–1589CrossRefPubMed
go back to reference Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290(5497):1779–1782CrossRefPubMed Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290(5497):1779–1782CrossRefPubMed
go back to reference Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch UK, Mack M, Heikenwalder M, Bruck W, Priller J, Prinz M (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10(12):1544–1553CrossRefPubMed Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch UK, Mack M, Heikenwalder M, Bruck W, Priller J, Prinz M (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10(12):1544–1553CrossRefPubMed
go back to reference Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 9(4):448–452CrossRefPubMed Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 9(4):448–452CrossRefPubMed
go back to reference Pessac B, Godin I, Alliot F (2001) Microglia: origin and development. Bull Acad Natl Med 185(2):337–346 (discussion 346–337)PubMed Pessac B, Godin I, Alliot F (2001) Microglia: origin and development. Bull Acad Natl Med 185(2):337–346 (discussion 346–337)PubMed
go back to reference Petito CK, Torres-Munoz JE, Zielger F, McCarthy M (2006) Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome. J Neurovirol 12(4):272–283CrossRefPubMed Petito CK, Torres-Munoz JE, Zielger F, McCarthy M (2006) Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome. J Neurovirol 12(4):272–283CrossRefPubMed
go back to reference Priller J, Flugel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernandez-Klett F, Prass K, Bechmann I, de Boer BA et al (2001) Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med 7(12):1356–1361CrossRefPubMed Priller J, Flugel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernandez-Klett F, Prass K, Bechmann I, de Boer BA et al (2001) Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med 7(12):1356–1361CrossRefPubMed
go back to reference Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, Huxham L, Minchinton AI, Mui A, Krystal G (2005) SHIP represses the generation of alternatively activated macrophages. Immunity 23(4):361–374CrossRefPubMed Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, Huxham L, Minchinton AI, Mui A, Krystal G (2005) SHIP represses the generation of alternatively activated macrophages. Immunity 23(4):361–374CrossRefPubMed
go back to reference Rezai-Zadeh K, Gate D, Szekely CA, Town T (2009a) Can peripheral leukocytes be used as Alzheimer’s disease biomarkers? Expert Rev Neurother 9(11):1623–1633CrossRefPubMed Rezai-Zadeh K, Gate D, Szekely CA, Town T (2009a) Can peripheral leukocytes be used as Alzheimer’s disease biomarkers? Expert Rev Neurother 9(11):1623–1633CrossRefPubMed
go back to reference Rezai-Zadeh K, Gate D, Town T (2009b) CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J Neuroimmune Pharmacol 4(4):462–475CrossRefPubMed Rezai-Zadeh K, Gate D, Town T (2009b) CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J Neuroimmune Pharmacol 4(4):462–475CrossRefPubMed
go back to reference Schleicher U, Hesse A, Bogdan C (2005) Minute numbers of contaminant CD8+ T cells or CD11b+CD11c+ NK cells are the source of IFN-gamma in IL-12/IL-18-stimulated mouse macrophage populations. Blood 105(3):1319–1328CrossRefPubMed Schleicher U, Hesse A, Bogdan C (2005) Minute numbers of contaminant CD8+ T cells or CD11b+CD11c+ NK cells are the source of IFN-gamma in IL-12/IL-18-stimulated mouse macrophage populations. Blood 105(3):1319–1328CrossRefPubMed
go back to reference Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81(2):741–766PubMed Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81(2):741–766PubMed
go back to reference Shaftel SS, Carlson TJ, Olschowka JA, Kyrkanides S, Matousek SB, O’Banion MK (2007a) Chronic interleukin-1 beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood brain barrier permeability without overt neurodegeneration. J Neurosci 27(35):9301–9309CrossRefPubMed Shaftel SS, Carlson TJ, Olschowka JA, Kyrkanides S, Matousek SB, O’Banion MK (2007a) Chronic interleukin-1 beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood brain barrier permeability without overt neurodegeneration. J Neurosci 27(35):9301–9309CrossRefPubMed
go back to reference Shaftel SS, Kyrkanides S, Olschowka JA, Miller JN, Johnson RE, O’Banion MK (2007b) Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest 117(6):1595–1604CrossRefPubMed Shaftel SS, Kyrkanides S, Olschowka JA, Miller JN, Johnson RE, O’Banion MK (2007b) Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest 117(6):1595–1604CrossRefPubMed
go back to reference Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49(4):489–502CrossRefPubMed Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49(4):489–502CrossRefPubMed
go back to reference Stalder AK, Ermini F, Bondolfi L, Krenger W, Burbach GJ, Deller T, Coomaraswamy J, Staufenbiel M, Landmann R, Jucker M (2005) Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice. J Neurosci 25(48):11125–11132CrossRefPubMed Stalder AK, Ermini F, Bondolfi L, Krenger W, Burbach GJ, Deller T, Coomaraswamy J, Staufenbiel M, Landmann R, Jucker M (2005) Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice. J Neurosci 25(48):11125–11132CrossRefPubMed
go back to reference Stoll G, Jander S (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58(3):233–247CrossRefPubMed Stoll G, Jander S (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58(3):233–247CrossRefPubMed
go back to reference Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ (2004) Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 172(7):4410–4417PubMed Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ (2004) Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 172(7):4410–4417PubMed
go back to reference Tanzi RE, Bertram L (2005) Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120(4):545–555CrossRefPubMed Tanzi RE, Bertram L (2005) Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120(4):545–555CrossRefPubMed
go back to reference Town T (2009) Alternative Abeta immunotherapy approaches for Alzheimer’s disease. CNS Neurol Disord Drug Targets 8(2):114–127CrossRefPubMed Town T (2009) Alternative Abeta immunotherapy approaches for Alzheimer’s disease. CNS Neurol Disord Drug Targets 8(2):114–127CrossRefPubMed
go back to reference Town T, Tan J, Flavell RA, Mullan M (2005) T-cells in Alzheimer’s disease. Neuromolecular Med 7(3):255–264CrossRefPubMed Town T, Tan J, Flavell RA, Mullan M (2005) T-cells in Alzheimer’s disease. Neuromolecular Med 7(3):255–264CrossRefPubMed
go back to reference Town T, Laouar Y, Pittenger C, Mori T, Szekely CA, Tan J, Duman RS, Flavell RA (2008) Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 14(6):681–687PubMed Town T, Laouar Y, Pittenger C, Mori T, Szekely CA, Tan J, Duman RS, Flavell RA (2008) Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 14(6):681–687PubMed
go back to reference Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E (2009) Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homing. Immunity 30(2):242–253CrossRefPubMed Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E (2009) Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homing. Immunity 30(2):242–253CrossRefPubMed
go back to reference Walker WS (1999) Separate precursor cells for macrophages and microglia in mouse brain: immunophenotypic and immunoregulatory properties of the progeny. J Neuroimmunol 94(1–2):127–133CrossRefPubMed Walker WS (1999) Separate precursor cells for macrophages and microglia in mouse brain: immunophenotypic and immunoregulatory properties of the progeny. J Neuroimmunol 94(1–2):127–133CrossRefPubMed
go back to reference Wenkel H, Streilein JW, Young MJ (2000) Systemic immune deviation in the brain that does not depend on the integrity of the blood–brain barrier. J Immunol 164(10):5125–5131PubMed Wenkel H, Streilein JW, Young MJ (2000) Systemic immune deviation in the brain that does not depend on the integrity of the blood–brain barrier. J Immunol 164(10):5125–5131PubMed
go back to reference Whitton PS (2007) Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol 150(8):963–976CrossRefPubMed Whitton PS (2007) Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol 150(8):963–976CrossRefPubMed
go back to reference Wisniewski HM, Wegiel J, Wang KC, Kujawa M, Lach B (1989) Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci 16(4 Suppl):535–542PubMed Wisniewski HM, Wegiel J, Wang KC, Kujawa M, Lach B (1989) Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci 16(4 Suppl):535–542PubMed
go back to reference Wisniewski HM, Barcikowska M, Kida E (1991) Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques. Acta Neuropathol 81(5):588–590CrossRefPubMed Wisniewski HM, Barcikowska M, Kida E (1991) Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques. Acta Neuropathol 81(5):588–590CrossRefPubMed
go back to reference Wyss-Coray T (2006) Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 12(9):1005–1015PubMed Wyss-Coray T (2006) Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 12(9):1005–1015PubMed
go back to reference Yong VW, Rivest S (2009) Taking advantage of the systemic immune system to cure brain diseases. Neuron 64(1):55–60CrossRefPubMed Yong VW, Rivest S (2009) Taking advantage of the systemic immune system to cure brain diseases. Neuron 64(1):55–60CrossRefPubMed
Metadata
Title
Macrophages in Alzheimer’s disease: the blood-borne identity
Authors
David Gate
Kavon Rezai-Zadeh
Dominique Jodry
Altan Rentsendorj
Terrence Town
Publication date
01-08-2010
Publisher
Springer Vienna
Published in
Journal of Neural Transmission / Issue 8/2010
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-010-0422-7

Other articles of this Issue 8/2010

Journal of Neural Transmission 8/2010 Go to the issue

Movement Disorders-Review Article

Inflammation processes in perinatal brain damage

Basic Neurosciences, Genetics and Immunology - Review Article

The role of microglia in amyloid clearance from the AD brain

Basic Neurosciences, Genetics and Immunology - Review article

Neuroinflammatory processes in Alzheimer’s disease

Movement Disorders - Review Article

Neuroinflammation in Huntington’s disease

Editorial

Editorial